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Jay Killian (Charles Bronson) is a senior member of the Secret Service. On the day before the Inauguration of the new president, Killian has just returned from a six-month sick leave. He is given a new assignment: to protect the First Lady, Lara Royce Craig (Jill Ireland).

Being highly qualified and a seasoned veteran of the service, Killian is dismayed that he is not on the Presidential detail. To make matters worse, Lara proves to be an extremely difficult charge. She is arrogant, condescending, demanding, and she detests the presence of Killian.

With the First Lady doing what she wants and ignoring all of Killian's suggestions, it becomes apparent that someone wants Lara dead—especially when a biker tries to shoot her.

A wild cross-country adventure ensues as Killian attempts to protect Lara and flush out the assassin and his contractor—and the assassination attempts may have originated from the White House.
It turns out that, because of a war injury, the President is impotent and that his wife is about to file in a divorce at the end of his first term. Believing that the divorce will eliminate the chances of another term, the president's right-sided supporters staged the assassination attempts, to keep the President's impotence a secret and gain him the peoples support in his grief.

The film was Jill Ireland's first in three years following an operation for breast cancer. It was originally called My Affair With the President's Wife, then The President's Wife and finally, Assassination. "Someone thought the original title might be insulting to the presidency of the United States, so they changed it," said Bronson "There's an assassination involved so they stuck with that. They didn't want to scare off people who come to see my films with a title like President's Wife. It's not what people expect from one of my pictures."[4]